Fig. 2

Schematic representation of extracellular and intracellular barriers to DNA delivery. DNA and DNA complexes delivered in vivo must overcome a number of barriers to achieve successful gene expression in the cell nucleus: (i) Endo and exonuclease degradation of DNA; (ii) Migration of DNA from the target tissue into systemic circulation; (iii) Binding and aggregation of DNA via serum protein complexation; (iv) Immune activation to delivered DNA; (v) Interaction and binding with erythrocytes; (vi) Clearance of DNA via spleen, renal and hepatic systems; (vii) Migration of DNA through extracellular matrix in target organ; (viii) Cellular uptake, mediated via endocytosis or passive entry; (ix) enzymatic degradation of DNA in lysosome; (x) Nuclear localization of DNA for protein expression